Risk Factors of Isolated Microtia: A Systematic Review and Meta-Analysis

Abstract

Background: Isolated microtia is a congenital facial anomaly, and its cause is unclear. This study systematically investigated related suspicious factors. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Four databases were searched for eligible case-control and cohort studies. Odds ratios and 95% confidence intervals were calculated for each exposure variable if data from at least two eligible studies were provided. If not, narrative syntheses were performed. Results: Twenty-eight articles were included. Meta-analyses were conducted with 22 articles, and 25 factors were identified to have significant association with isolated microtia. Moderate evidence showed that parental low education level, low birth weight (<2500 g), parity greater than or equal to 2, and family history of malformation (especially microtia); maternal intake of antibiotics, benzodiazepines, nonsteroidal antiinflammatory drugs, progesterone, and traditional Chinese medicine; in addition to maternal nongestational diabetes, upper respiratory infection, and radiation exposure increased the risk of microtia in offspring. Limited evidence showed that maternal Hispanic race, pesticide exposure, threatened abortion, history of spontaneous abortion, pet contact, and male gender were associated with increased risk. Maternal race of black or non-Hispanic, and living in an urban area were two protective factors found with moderate and limited evidence, respectively. Conclusion: This study has provided an initial investigation of potential factors associated with isolated microtia and evidence-based conclusion supporting prevention of modifiable factors.

BMP signaling maintains auricular chondrocyte identity and prevents microtia development by inhibiting protein kinase A

“…Microtia is usually a congenital disorder that affects the hearing and psychological health of affected children. Many of the disease-candidate genes are involved in the proliferation and differentiation of auricle chondrocytes and, therefore, the development or growth of auricle cartilage ( Gendron et al, 2016 ; Huang et al, 2023 ). Here, we show that in young or adult mice, ablation of Bmpr1a in auricle chondrocytes, which are genetically labeled by Prrx1 , leads to rapid development of microtia.…”

“…Microtia causes hearing problems and delays in language learning ( Gendron et al, 2016 ). Genetic studies have shown that microtia is linked to mutations in ROBO1/ROBO2 , HOXA2 , SIX1/SIX5 , TBX1 , or CHUK in humans ( Cox et al, 2014 ; Huang et al, 2023 ; Lu et al, 2020 ; Quiat et al, 2022 ). In mice, Prrx1 and Prrx2, FGF, BMP, and Wnt have been shown to affect auricle development ( ten Berge et al, 1998 ; Xie et al, 2020 ).…”

BMP signaling maintains auricular chondrocyte identity and prevents microtia development by inhibiting protein kinase A

“…Microtia is usually a congenital disorder that affects the hearing and psychological health of affected children. Many of the disease candidate genes are involved in the proliferation and differentiation of auricle chondrocytes and therefore the development or growth of auricle cartilage (Gendron et al, 2016; Huang et al, 2023). Here, we show that in young or adult mice, ablation of Bmpr1a in auricle chondrocytes, which are genetically labelled by Prrx1 , leads to rapid development of microtia.…”

“…Microtia causes hearing problems and delays in language learning (Gendron et al, 2016). Genetic studies have shown that microtia is linked to mutations in ROBO1/ROBO2 , HOXA2 , SIX , TBX1 , or CHUK in humans (Cox et al, 2014; Huang et al, 2023; Lu et al, 2020; Quiat et al, 2022). In mice, Prrx1 and Prrx2, FGF, BMP, and Wnt have been shown to affect auricle development (ten Berge et al, 1998; Xie et al, 2020).…”

Genetics and Epigenetics in the Genesis and Development of Microtia

“…Inherited defects, external factors, or the interaction between genes and external factors are the main causes of microtia. Epidemiological studies have found that environmental factors, including cold-like syndromes during pregnancy, a history of spontaneous abortion, vaginitis, cervicitis, and other infections, as well as exposure to toxic chemicals, such as polycyclic aromatic hydrocarbons, paints, and pesticides, are risk factors for the disease 6 . Evidence that strongly suggests a genetic cause for microtia includes the higher frequency of cases in monozygotic twins (38.5%) compared with dizygotic twins (4.5%); reporting of familial cases with autosomal recessive or dominant inheritance patterns linked to variable expression and incomplete penetrance; family history of disease in about 3% to 34% of cases; reporting of >18 different microtia-related syndromes, which include those associated with monogenic defects or chromosomal aberrations; and mouse models proving the genetic cause microtia 4 .…”